The kidney plays important roles in the excretion of endogenous compounds and xenobiotics. Anionic substances including drugs are excreted via carrier-mediated pathway(s) into the urine. The first step of this secretion is the uptake of organic anion from the peritubular plasma across the basolateral membrane of the proximal tubule cells.
The basolateral uptake of the organic anions has been studied using several techniques, such as perfusion of excised kidney, or membrane vesicles of isolated tubule cells. In these studies, para-aminohippurate (PAH) has been widely used as a test substrate. During these studies, it has been supposed that the organic anion transporter responsible for the basolateral uptake of organic anions was an organic anion/dicarboxylate exchanger.
There are, however, limitations in the previous techniques for precise analysis of the organic anions transport, such as the networks of transport between different transporters and the drug—drug interaction against a single molecule. Thus, the isolation of the organic anion transporter molecule which enables more precise analysis of the organic anion transporter has been eagerly awaited.
So far, several transporter molecules which are expressed in the liver have been isolated (Hagenbuch, B. et al. Proc. Natl. Acad. Sci. U.S.A. 88, 10629–10633, 1991, Jacquemin, E. et al. Proc. Natl. Acad. Sci. U.S.A. 91, 133–137, 1994). The cDNA cloning of organic cation transporter (OCT1), which is expressed in the kidney and the liver, was also reported (Grundemann, D. et al. Nature 372, 549–52, 1994).
As a sodium-dependent dicarboxylate cotransporter, the cDNA encoding sodium-dicarboxylate co-transporter (NaDC-1) was reported (Pajor, A. M. J. Biol. Chem. 270, 5779–5785, 1995).
Recently, OAT-K1, an isoform of oatp was isolated (Saito, H. et al. J. Biol. Chem. 271, 20719–20725, 1996). Oatp is organic anion transporting polypeptide which is expressed in the liver and mediates the sodium-independent transport of organic anions. OAT-K1 is expressed in the renal proximal tubules, however, the transport properties of OAT-K1 was distinct from that of the organic anion/dicarboxylate exchanger of the renal proximal tubule cells.